Process for the preparation of chromene derivatives

ABSTRACT

The invention relates to a process for the preparation of Chromenes of the general Formula V ##STR1## prepared from chromanone derivatives.

RELATED U.S. APPLICATION DATA

This is a continuation of co-pending application Ser. No. 06/919,267filed on Oct. 16, 1986 and now abandoned, which is a division of Ser.No. 07/166,806 filed Mar. 3, 1988 and now U.S. Pat. No. 4,866,089, whichis a continuation of Ser. No. 06/908,946 filed Sept. 16, 1986 and nowabandoned, which is a continuation of Ser. No. 06/580,647 filed Feb. 16,1984 and now abandoned.

FIELD OF THE INVENTION

The invention relates to partly new and partly known chromenederivatives, a process for the preparation thereof and pesticidalcompositions comprising the same.

The said chromene derivatives are analogues of7-methoxy-2,2-dimethyl-2H-chromene Precocene-1 (P1) and6,7-dimethyl-2H-chromene Precocene-2 (P2) isolated from nature.

BACKGROUND OF THE INVENTION

The so-called Precocene-1 (P1) and Precocene-2 (P2) are known substancesisolated from natural sources. Bowers et al. reported about thebiological effects of P1 and P2 [W. S. Bowers, T. Ohta et al.: Science193, 542 (1976)]. On the basis of this biological activity it could beexpected that P1 and P2 would be useful as a new-type pesticide causingno environmental pollution.

Several articles are published on the biological activity, mechanism ofaction and metabolism of precocenes. It is known that these compoundsexhibit their action by damaging the juvenile hormone producing organ ofinsects, i.e. by special injury of the so-called "corpora allata". Ontesting the effects of the substances isolated from nature thecorrelation between the given biological group of effects and the2H-chromene ring-system was studied. According to experimental resultsthe character and strength of the activity of precocenes depends to alarge extent on the pest species, the test method used and from thepoint of view of chemical structure probably on the number and positionof the substituents of the aromatic ring, the strength of the doublebond of the pyrane ring and on the electronic and steric parameters ofthe complete molecule [W. S. Bowers; Martinez-Paro, R.: Science 197 1369(1977); H. Schooneveld: Experientia 35 363 (1979); W. S. Bowers: Pontif.Acad. Sci. Scr. Varia 41 129 (1976); G. T. Brooks et al.: Nature 281 570(1979); T. Ohta: Kagaku to Seibutsu 17(2) 92 (1979); T. Ohta: Konchu noSeiri to Kagaku 63 (1979); G. Matolcsy et al.: Z. Naturforsch. 35b. 1449(1980); G. T. Brooks et al.: Proc. Br. Crop. Prot. Conf. Pests. Dis. 1273 (1979); G. E. Pratt et al.: Nature 284 320 (1980); D. M. Soderlundet al.: J. Agr. Food Chem. 28(4) 724 (1980); D. A. Schooley et al.:Pestic. Biochem. Physiol. 13(2) 95 (1980); A. P. Ottridge et al.:Pestic. Sci. 12(3) 245 (1981)].

As a result of the above research work a number of derivatives beingmore active than P1 and P2 occurring in nature were obtained, e.g.6-methoxy-7-ethoxy-2,2-dimethyl-2H-chromene (Precocene 3, P3, 3623)which is ten times more effective than P2.

In the published articles and patent specifications relatively fewanalogue compound--about 80-100 derivatives--are disclosed, although theprecise study of correlations between biological activity and chemicalstructure and the selection of the most active derivatives would requiremuch more compounds. This is probably due to the fact that the knownsynthesis are very complicated.

According to prior art [CHROMENES CHROMANONES and CHROMONES, Edited byG. P. Ellis: John Wiley and Sons London, pages 43-63, (1977)] severalroutes are known for the preparation of 2H-chromene derivatives, thesaid routes being independent from each other. The majority of thesemethods is used for the preparation of P1 and P2 and analogues thereof[W. S. Bowers, T. Ohta: Chem. Pharm. Bull. 25(9) 2788 (1977); D. J.Gale, J. P. K. Wilshire: J. Text. Inst. 12 525 (1979); W. Biernacki, W.Sobotka: Polish J. Chem. 53 2275 (1979); 54 2239 (1980); G. Cardillio etal: Tetr. Lett. 27 2545 (1979); J. Chem. Soc. Shem. Comm. 836 (1979); F.Camps, et al.: Tetr. Lett. 40 3901 (1979); 21 2361 (1980); J. Het. Chem.17 207 and 1377 (1980); Tsukayama et al. Heterocycles 16(6) 955 (1981);A. Banerji, N. C. Goomer: Ind. J. Chem. 20B 144 (1981)].

The following patent specifications are published in this field GermanFederal Republic patent No. 2,639,671; U.S. Pat. No. 4,162,326; JapanesePat. Nos. 73121/79, 15,411/80, 40,637/80 and 43,039/80.

The common feature of the said patent specifications and otherpublications is that although different synthesis routes are used thepreparation of each analogue compound constitutes a specific problem andrequires the use of different starting materials.

Thus according to German Federal Republic patent No. 2,639,671 andJapanese patent Nos. 15,411/80 and 40,637/80 P2 is prepared from3,4-dimethoxy-phenol and P3 being ten times more active from3-ethoxy-4-methoxyphenol and the industrial scale production of the saidstarting materials in a sufficient amount and suitable purityconstitutes a rather complicated problem per se.

DISCLOSURE OF THE INVENTION

The present invention is based on the recognition that a large number ofbiologically active 2H-chromenes of the Formula V ##STR2## --themajority thereof being new compounds--can be prepared by starting fromthe suitably substituted hydroxy-4-chromanone derivative of the FormulaI. ##STR3##

The present invention relates to a new process for the preparation ofbiologically active chromene derivatives. The intermediates andendproducts prepared by the process of the present invention are partlynew compounds.

According to a feature of the present invention there is provided aprocess for the preparation of chromene derivatives of the Formula V.

According to a further feature of the present invention there areprovided new chromanone derivatives of the Formulae VI, VII, VIII, IX, Xand XI. ##STR4##

According to a still further feature of the present invention there areprovided new chromene derivatives of the Formulae XII, XIII, XIV, XV andXVI. ##STR5##

According to a still further feature of the present invention there areprovided pesticidal compositions comprising as active ingredient atleast one chromene derivative of the Formula V, particularly a chromenederivative of the Formula XII, XIII, XIV, XV and/or XVI.

In the above Formulae

R¹ and R² are hydrogen, optionally halogeno substituted C₁₋₆ alkyl oraryl;

R³ and R⁷ stand for hydrogen, halogen or C₁₋₆ alkyl;

R⁴ represents C₁₋₈ alkyl, aryl, aralkyl or a group containing a carbonylgroup;

R⁵ and R⁶ stand for C₁₋₁₀ alkyl, aryl, amino, hydroxyalkyl,alkoxyalkenyl, alkylmercaptoalkyl, acyl, carboxy or an ester group or ahalogen atom;

n is 0 or 1;

m is 1 or 2;

X stands for a halogen atom or a sulfonate, sulfate or epoxy group;

R⁸ and R⁹ are hydrogen, methyl, ethyl, trifluoromethyl or phenyl;

R¹⁰ is hydrogen, chlorine, fluorine, bromine or methyl;

R¹¹ and R¹² stand for hydrogen, methyl, acetyl or an aldehyde group;

R¹⁴, R¹⁵ and R¹⁸ are hydrogen or methyl;

R¹⁶ and R¹⁷ stand for hydrogen, chlorine or methyl.

The alkyl groups may be straight or branched chained.

According to the present invention there is provided a process for thepreparation of chromene derivatives of the Formula V which comprises

(a) for the preparation of compounds, in which R⁵ and R⁶ stand fordifferent groups, reacting a compound of the Formula I with anapproximately equimolar, preferably 0.8-1.5 molar amount of a reactantof the Formula R⁵ -X--related to the amount of the compound of theFormula I (wherein R⁵ has the same meaning as stated above and X ishalogen) and reacting the O-monosubstituted compound of the Formula III##STR6## wherein R¹ -R⁶ and n are as stated above) obtained with a1.1-1.5 molar amount of a compound of the Formula R⁶ -X related to theamount of the compound of the Formula III (wherein R⁶ and X are asstated above); or

(b) for the preparation of compounds, in which R⁵ and R⁶ stand for thesame group, reacting a chromanone of the Formula I (wherein R¹ -R⁴ and mhave the meaning as stated above) with a 2-3 molar amount of a compoundof the Formula R⁵ -X --related to the amount of the compound of FormulaI (wherein R⁵ and X are as stated above), preferably in the presence ofa base, a catalyst and a solvent, and thereafter reducing theO-substituted chromanone derivative of the Formula III thus obtained(wherein R¹ -R⁶ and n are as stated above) and dehydrating the chromanolderivative of the Formula IV ##STR7## thus obtained (wherein R¹ -R⁶ andn are as stated above) in acidic-aqueous medium.

Specific compounds within the scope of R⁵ -X and R⁶ -X alkylating oracylating agents, are a C₁ to C₆ alkyl, alkenyl, alkynyl, acyl,alkoxyalkyl or alkylmercaptoalkyl halides, preferably methyl, ethyl orisopropyl iodide; isopropyl, butyl or secondary butyl, allyl, butenyl,crotyl, or prenyl bromide; chloromethyl-thiomethyl ether orchloromethyl-ethyl ether and/or bromomethyl ethyl ether, a substitutedalkyl halide, preferably morpholinyl ethyl chloride, a diahlogenoalkylene, preferabl dimbromomethane, ethane, or propane, a dialkylsulfate, preferably dimethyl sulfate, a substituted alkyl or alkoxyalkyltosylate, preferably trifluoromethoxy tosylate, or an alkene oxide,preferably propene oxide.

The present invention is partly based on the important recognition thatthe hydroxy groups of the hydroxy-4-chromanone derivatives of theFormula I show different reactivity in O-substitution reactions as aresult of their interaction with the carbonyl group in position 4.

This difference can be strengthened by deliberate direction of thereaction conditions to such an extent that selective mono-O-substitutioncan be carried out with excellent yields. It has been confirmed byvarious measurements and calculations (PMR, CMR, UV-VLSspectrophotometrical and potentiometric acid-base titrations, pKdeterminations, "all valence" CNDO quantumchemical calculations.electrostatical potential map calculation) that the hydroxy group inposition 7 is the most reactive while the hydroxy groups in positions 5,6 and 8, respectively, are less reactive. The said difference isillustrated by the determined and calculated pK value summarized in thefollowing Table 1.

                  TABLE 1                                                         ______________________________________                                        Substituents   pK.sub.7 (1.)                                                                          pK.sub.7 (2.)                                                                          pK.sub.X (2.)                                ______________________________________                                        5-OH  7-OH     4-OH    7.4    7.0    11.6 (X = 5)                             6-OH  7-OH     4-H     6.8    6.9    11.4 (X = 6)                             8-OH  7-OH     4-H     7.2    7.2    11.6 (X = 8)                             ______________________________________                                         (1.) is determined by potentiometrical titration and                          (2.) according to spectrophotometrical measurement).                     

Thus when using 6,7-dihydroxy-2,2-dimethyl-4-chromanone the alkylationof the hydroxy group in position 7 c an be carried out selectively witha preparative yield of 90-95%. This enables the preparation of the6-hydroxy-7-alkoxy derivative and thereof by using other alkylating oracylating agents the preparation of "mixed" 6,7-dialkoxy-or 6acyloxy-7-alkoxy-chromanone derivatives.

INDUSTRIAL APPLICABILITY OF THE INVENTION

The invention enables the preparation of known precocenes and moreactive analogues thereof from easily available starting materials of thesame type by using cheap and known reactants. The present inventionprovides a simple industrial scale process which enables the use of thiscompound group in pharmaceutical industry both for synthetic andpharmacological purposes.

MODES OF CARRYING OUT OF THE INVENTION

Further details of the present invention are to be found in the Exampleswithout limiting the scope of protection to the said Examples.

The purity of the compounds disclosed in the Examples is determined bythin layer chromatographical and gas chromatographical methods. Thechemical structure of the compounds is confirmed by UV, IR, PMR and CMRspectra and occasionally by elementary analysis.

The PMR spectra are indicated as follows: e.g. 1.45 (3H; 5 t; J=5 Hz),

wherein

1.45=chemical shift

3H=number of protons belonging to the sign

t=multiplicity of the sign

J=coupling constant

designation of multiplets:

s=singulet

d=triplet

t=triplet

q=quartet

m=multiplet of higher order

sz=broad protracted sign.

PREPARATION OF COMPOUNDS OF THE FORMULA I, II (1) Preparation of6,7-dimethoxy-2,2-dimethyl-4-chromanone

In 100 ml of acetone 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved and to thesolution 8.3 g (60 millimoles) of potassium carbonate and 8.5 g (3.8 ml,60 millimoles) of methyl iodide are added. The reaction mixture isrefluxed for 7 hours whereupon a further amount of 2.8 g (1.2 ml, 20millimoles) of methyl iodide are added. The reaction mixture is heatedto boiling for 3 hours, the suspension formed is cooled under stirring,the precipitated inorganic salt is filtered off, washed twice with 20 mlof acetone each and the acetone is removed. The residue is crystallizedfrom 80% ethanol. Thus 4.5 g of the desired compound are obtained, yield95.2%. Mp.: 105°-106° C.

PMR (CDCl₃): 1.38 (6H; s); 2.64 (2H, s); 3.78 (3H, s); 3.86 (3H, s); 6.5(1H, s); 7.18 (1H, s).

EXAMPLE 2 Preparation of 6,7-dimethoxy-2,3-dimethyl-4-chromanone

In 80 ml of methyl-ethyl-ketone 4.2 g (20 millimoles) of6,7-dihydroxy-2,3-dimethyl-4-chromanone are dissolved. To the solution6.4 g (60 millimoles) of sodium carbonate and 8.5 g (3.8 ml, 60millimoles) of methyl iodide are added and the reaction mixture isrefluxed for 4 hours. After addition of a further 2.8 g (1.2 ml, 20millimoles) of methyl iodide the reaction mixture is refluxed foranother 3 hours. The reaction mixture is worked up according toExample 1. Thus, 4.3 g of the desired compound are obtained, yield91.0%. Mp.: 171°-172° C.

PMR (CDCl₃): 1.15 (3H, J=5 Hz); 1.45 (3H, d,J=5 Hz); 2.5 (1H, m); 3.8(3H, s); 3.84 (3H, s); 4.1 (1H, m); 6.32 (1H, s); 7.16 (1H, s).

EXAMPLE 3 Preparation of 5,7-dimethoxy-2,2-dimethyl-4-chromanone

In a mixture of 40 ml of acetone and 40 ml of methyl ethyl ketone 4.2 g(20 millimoles) of 5,7-dihydroxy-2,2-dimethyl-4-chromanone aredissolved, whereupon to the solution 8.3 g (60 millimoles) of potassiumcarbonate and 5.3 g (3.9 ml, 42 millimoles) of dimethyl sulfate areadded under stirring. The reaction mixture is refluxed for 8 hours, thesuspension is cooled under stirring, the precipitated inorganic salt isfiltered off, washed twice with 20 ml of acetone each and the solvent isremoved in vacuo. The residue is taken up in 100 ml of chloroform,washed subsequently with 50 ml of 2% sodium hydroxide solution and 50 mlof water, dried over sodium sulfate and the chloroform is removed invacuo. The residue is crystallized from 70% ethanol. Thus 4.4 g of thedesired compound are obtained, yield 93.1%. Mp.: 104°-105° C.

PMR (CDCl₃): 1.4 (6H, s); 2.56 (2H, s); 3.72 (3H, s); 3.8 (3H, s); 5.92(2H, m).

EXAMPLE 4 Preparation of 7,8-dimethoxy-2,2-dimethyl-4-chromanone

In 50 ml of N,N-dimethyl-formamide 4.2 g (20 millimoles) of7,8-dihydroxy-2,2-dimethyl-4-chromanone are dissolved and to thesolution 6.4 g (60 millimoles) of sodium carbonate and 5.3 g (3.9 ml (42millimoles) of dimethyl sulfate are added under stirring. The reactionmixture is stirred at 120° C. for 5 hours, poured onto 150 g of crushedice and extracted three times with 50 ml of chloroform each. The organicphase is washed three times with 100 ml of water each, dried over sodiumsulfate and the solvent is distilled off. The residue is crystallizedfrom 75% methanol. Thus 4.0 g of the desired compound are obtained,yield 84.6%. Mp.: 75°-76° C.

PMR (CDCl₃): 1.42 (6H, s); 2.64 (2H, s); 3.8 (3H, s); 3.88 (3H, s); 6.56(1H, d, J=8 Hz); 7.6 (1H, d, J=8 Hz).

EXAMPLE 5 Preparation of 7-methoxy-2,2-dimethyl-4-chromanone

In 40 ml of 5% sodium hydroxide solution 3.84 g (20 millimoles) of7-hydroxy-2,2-dimethyl-4-chromanone are dissolved whereupon 80 ml ofdichloro methane and 0.5 g of triethyl benzyl ammonium chloride areadded and the mixture is intensively stirred at room temperature for 20minutes. After addition of 4.25 g (1.9 ml, 30 millimole) of methyliodide the reaction mixture is stirred for 2 hours. The organic layer isseparated, washed twice with 50 ml of water each, dried over sodiumsulfate and evaporated. The residue is crystallized from 80% methanol.Thus 3.9 g of the desired compound are obtained, yield 94.6%. Mp.77°-78° C.

PMR (CDCl₃): 1.38 (6H, s); 2.6 (2H, s); 3.74 (3H, s); 6.3 (1H, d, J=2Hz); 6.44 (1H, dd, J=8 Hz, respectively J=2 Hz); 7.7 (1H, d, J=8 Hz).

EXAMPLE 6 Preparation of 7-methoxy-2,2,5-trimethyl-4-chromanone

In 50 ml of acetonitrile 4.9 g (20 millimoles) of the potassium salt of7-hydroxy-2,2,5-trimethyl-4-chromanone are dissolved and the solution isstirred in the presence of 0.5 g (2 millimoles) of 18-Crown-6 at roomtemperature for 30 minutes. To the mixture 4.25 g (1.9 ml, 30millimoles) of methyl iodide are added and the reaction mixture isstirred for a further hour. The inorganic salt is filtered off and thesolvent is removed. The residue is taken up in chloroform, washed twicewith 50 ml of water each, dried over sodium sulfate and evaporated. Theproduct is crystallized from 90% ethanol. Thus 3.75 g of the desiredcompound are obtained, yield 85%. Mp.: 86°-88° C.

PMR (CDCl₃): 1.36 (6H, s); 2.52 (3H, s); 2.56 (2H, s); 3.7 (3H, s); 6.2(2H, m).

EXAMPLE 7 Preparation of 7-methoxy-2,2,8-trimethyl-4-chromanone

The reaction is carried out under nitrogen. In 50 ml of a 10% sodiumhydroxide solution 4.9 g (23.8 millimoles) of7-hydroxy-2,2,8-trimethyl-4-chromanone are dissolved, 2.6 g (2 ml, 21millimoles) of dimethyl sulfate are added and the reaction mixture isvigorously stirred for 2 hours. The reaction mixture is diluted with 100ml of icecold water and extracted three times with 50 ml of carbontetrachloride each. The organic phase is washed twice with 50 ml ofwater each, dried over sodium sulfate, the solvent is removed and theresidue crystallized from 90% methanol. Thus 3.4 g of the desiredcompound are obtained, yield 78%. Mp.: 105°-107° C.

PMR (CDCl₃): 1.45 (6H, s); 2.07 (3H; s); 2.67 (2H; s); 3.90 (3H, s);6.57 (1H; d; J=10 Hz); 7.77 (1H; J=10 Hz).

EXAMPLE 8 Preparation of 6,7-methylenedioxy-2,2-dimethyl-4-chromanone

A mixture of 20 ml of water, 5.2 g (30 millimole) of dibromo-methane and0.5 g (1 millimole) of Adogen 464 (Aldrich) is heated to boiling undervigorous stirring. A solution of 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone and 50 ml of a 5% sodiumhydroxide solution is added dropwise within 2 hours and heated toboiling for a further hour. The mixture is diluted with 100 ml of waterand extracted twice with 50 ml of chloroform each. The organic layer iswashed twice with 50 ml of water, dried over sodium sulfate, the solventis removed and the residue crystallized from hexane. Thus 3.6 g of thedesired compound are obtained, yield 85%. Mp: 61°-62° C.

PMR (CDCl₄): 1.42 (6H, s); 2.56 (2H, s); 6.0 (2H, s); 6.32 (1H, s); 7.14(1H, s).

EXAMPLE 9 Preparation of 6,7-ethylenedioxy-2,2-dimethyl-4-chromanone

To a stirred mixture of 100 ml of methyl-ethylketone and 2.6 ml (30millimoles) of 1,2-dibromo ethane heated to 60° C. 4.2 g (20 millimoles)of 6,7-dihydroxy-2,2-dimethyl-4-chromanone and a suspension of 8.3 g (60millimoles) of potassium carbonate and 0.5 g of potassium iodide in 100ml of methyl-ethyl ketone are added dropwise within 3 hours. Thereaction mixture is heated to boiling for 5 hours. The inorganic salt isfiltered off, washed twice with 20 ml of acetone each and the solvent isremoved. The residue is crystallized from 70% ethanol. Thus, 3.75 g ofthe desired compound are obtained, yield 80%. Mp.: 118°-119° C.

PMR (CDCl₃): 1.36 (6H, s); 2.58 (2H, s); 4.2 (4H, m); 6.36 (1H, s); 7.3(1H, s).

EXAMPLE 10 Preparation of6,7-(1,3-propylenedioxy)-2,2-dimethyl-4-chromanone

In 50 ml of N,N-dimethyl-formamide 6 g (3 ml, 30 millimoles) of1,3-dibromo-propane are dissolved. The solution is heated to 120° C. andat this temperature a suspension of 4.2 g of6,7-dihydroxy-2,2-dimethyl-4-chromanone, 8.3 g (60 millimoles) ofpotassium carbonate, 0.5 g of potassium iodide and 50 ml of N,N-dimethylformamide is added within 3 hours dropwise. The reaction mixture isheated at 120° C. for a further 2 hours and worked up according toExample 8. Thus 3.7 g of the desired compound are obtained in the formof a yellow oil. Yield 75%.

PMR (CDCl₃): 1.36 (6H, s); 2.1 (2H, m); 2.58 (2H, s); 4.2 (4H, m); 6.4(1H, s); 7.36 (1H, s).

EXAMPLE 11 Preparation of6,7-bis-(trifluoroethoxy)-2,2-dimethyl-4-chromanone

In 100 ml of N,N-dimethyl-formamide 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved under nitrogenwhereupon 8.3 g (60 millimoles) of potassium carbonate and 11.5 g (45millimoles) of trifluoroethoxy tosylate are added. The reaction mixtureis stirred at 120° C. for 10 hours, poured onto 200 ml of crushed ice,100 ml of saturated sodium hydrogen carbonate solution are added and themixture is extracted three times with 50 ml of carbon tetrachlorideeach. The organic phase is washed twice with 100 ml of water each, driedover anhydrous sodium sulfate and the solvent is removed. The residue iscrystallized from ethanol. Thus 4.8 g of the desired compound areobtained, yield 65%. Mp.: 92°-93° C.

PMR (CDCl₃): 1.48 (6H, s); 2.7 (2H, s); 4.35 (4H, m); 6.5 (1H, s); 7.48(1H, s).

    ______________________________________                                        Analyses:                                                                               calculated %                                                                           found %                                                    ______________________________________                                        C           48.44      48.39; 48.25                                           H           3.81       3.79; 3.72                                             F           30.56      30.62; 30.55.                                          ______________________________________                                    

EXAMPLE 12 Preparation of 7-methoxymethoxy-2,2-dimethyl-4-chromanone

A mixture of 20 ml of 10% sodium hydroxide solution, 50 ml of dichloromethane, 0.5 g (2 millimoles) of triethyl benzyl ammonium chloride and0.9 g (10 millimoles) of 7-hydroxy-2,2-dimethyl-4-chromanone isintensively stirred at 20° C. for 30 minutes. To the mixture 3.1 g (2ml, 25 millimoles) of bromomethyl-methyl-ether are added. The reactionmixture is stirred for a further 30 minutes, the organic phase isseparated, washed twice with 50 ml. of water each, dried and the solventis removed. The residue is crystallized from 70% ethanol. Thus 2.1 g ofthe desired compound are obtained, yield 90% . Mp.: 77°-79° C.

PMR (CDCl₃): 1.38 (6H, s); 2.6 (2H, s); 3.4 (3H, s); 5.1 (2H, s); 6.5(2H, m); 7.7 (1H, d, J=8 Hz).

EXAMPLE 13 Preparation of 7-ethoxymethoxy-2,2-dimethyl-4-chromanone

A mixture of 40 ml of an 5% sodium hydroxide solution, 60 ml of dichloromethane, 0.5 g (2 millimoles) of triethyl benzyl aminium chloride and1.9 g (10 millimoles) of 7-hydroxy-2,2-dimethyl-4-chromanone isintensively stirred at room temperature for 20 minutes, whereupon 2.3 g(2,2 ml, 25 millimoles) of chloromethyl-ethyl-ether are added and thereaction mixture is stirred for an hour. The reaction mixture is workedup according to Example 12. Thus 2.1 g of the desired compound areobtained in the form of a light yellow oil, yield 85%.

PMR (CDCl₃): 1.16 (3H, t, J=7 Hz); 1.4 (6H, s); 2.6 (2H, s); 3.66 (2H,q, J=2 Hz); 5.14 (2H, s); 6.5 (2H, m); 7.7 (1H, d, J=8 Hz).

EXAMPLE 14 Preparation of7-(methylmercapto-methoxy)-2,2-dimethyl-4-chromanone

A mixture of 20 ml of a 10% sodium hydroxide solution, 40 ml ofdichloromethane, 0.5 g (2 millimoles) oftetrabutyl-ammonium-hydrogensulfate and 10 millimoles of7-hydroxy-2,2-dimethyl-4-chromanone is intensively stirred for 30minutes. To the mixture 2.4 g (2.1 ml, 25 millimoles) ofchloromethyl-thiomethyl-ether are added, the reaction mixture is stirredfor 20 minutes at room temperature and worked up according to Example12. Thus 2.0 g of the desired compound are obtained in the form of anorange oil, yield 79%.

PMR (CDCl₃): 1.36 (6H, s); 2.18 (3H, s); 2.6 (2H, s); 5.1 (2H, s); 6.36(1H, d, J=2 Hz); 6.5 (1H, dd, J=2 Hz, respectively J=8 Hz); 7.7 (1H, d,J=8 Hz).

EXAMPLE 15 Preparation of7-(2-hydroxy-n-propoxy)-2,2-dimethyl-4-chromanone

To a mixture of 40 ml of methanol, 5 ml of water 1.1 g (20 millimoles)of potassium hydroxide and 3.8 g (20 millimoles) of7-hydroxy-2,2-dimethyl-4-chromanone under stirring 11.6 g (14 ml, 0.2mole) of propene oxide are added and the reaction mixture is refluxedfor 5 hours. The reaction mixture is diluted with 200 ml of water andworked up according to Example 12. Thus 4.0 g of the desired compoundare obtained, yield 80%. Mp.: 111°-113° C.

PMR (acetone-d₆): 1.12 (3H, d, J=4 Hz); 1.36 (6H, s); 2.6 (2H, s); 3.9(2H, d, J=5 Hz); 4.2 (2H, m+s); 6.34 (1H, d, J=2 Hz); 6.5 (1H, dd, J=2Hz, respectively J=8 Hz); 7.7 (1H, d, J=8 Hz).

EXAMPLE 16 Preparation of 7-morpholinyl-ethoxy-2,2-dimethyl-4-chromanone

In 100 ml of methyl-ethyl-ketone 3.8 g (20 millimoles) of7-hydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 8.3 g (60millimoles) of potassium carbonate, 0.5 g potassium iodide andthereafter 4.6 g (25 millimoles) of morpholinyl-ethyl-chloridehydrochloride are added and the reaction mixture is heated to boilingfor 10 hours. The reaction having been completed the reaction mixture iscooled, the inorganic salt filtered off, washed twice with 20 ml ofacetone each and the solvent is removed. The residue is treated with 100ml of water. Thus 5.2 g of the desired compound are obtained in the formof white crystals, yield 85.3%. Mp.: 61°-63° C.

PMR (CDCl₄): 1.36 (6H, s); 2.5 (6H, m); 2.7 (2H, t, J=5 Hz); 3.54 (4H,m); 4.0 (2H, t, J=5 Hz); 6.2 (1H, d, J=2 Hz); 6.35 (1H, dd, J=2 Hz,respectively J=8 Hz); 7.6 (1H, d, J=8 Hz).

Preparation of compounds of the Formula II ##STR8## EXAMPLE 17Preparation of 6-hydroxy-7-methoxy-2,2-dimethyl-4-chromanone

In 100 ml of acetone 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved and to thesolution thus obtained 4.1 g (30 millimoles) of potassium carbonate and4.5 g (2 ml, 30 millimole) of methyl iodide are added under stirring.The reaction mixture is refluxed for 4 hours. The inorganic salt isfiltered off, washed twice with 20 ml of acetone each and the solvent isremoved. The residue is suspended in 100 ml of chloroform and extractedtwice with 50 ml of a 4% sodium hydroxide solution each. Theaqueous-alkaline phase is separated, cooled to 5° C. and acidified with37% hydrochloric acid under constant stirring. The precipitated productis filtered off, washed twice with 20 ml of water each and dried toconstant weight. The product is purified by recrystallization fromanhydrous ethanol. Thus 4.0 g of the desired compound are obtained,yield 90%. Mp.: 134°-136° C.

IR (CCl₄): νCO: 1690 cm⁻¹ ; νOH: 3570 cm⁻¹.

PMR (CDCl₃): 1.4 (6H, s); 2.62 (2H, s); 3.88 (3H, s); 6.42 (2H, s+s);7.36 (1H, s).

EXAMPLE 18 Preparation of 6-hydroxy-7-ethoxy-2,2-dimethyl-4-chromanone

In 100 ml of methyl-ethyl-ketone 4.2 g (2 (20 millimoles) of6,7-dihydroxy-2,2-dimenthyl-4chromanone are dissolved. To the solution4.1 (30 millimoles) of potassium carbonate and 4.7 g (2.4 ml, 30millimoles) of ethyl iodide are added and the reaction mixture is heatedto boiling for 3 hours. The reaction mixture is worked up according toExample 17. Thus 4.0 g of the title compound are obtained, yield 85%.Mp.: 129°-130° C.

IR: (CCl₄): νCO: 1690 cm⁻¹ ; νOH 3570 cm⁻¹.

PMR (CDCl₃): 1.5 (9H, m); 2.64 (2H, s); 4.18 (2H, q, J=J=3 Hz); 6.41(2H, s+s); 7.4 (1H, s).

EXAMPLE 19 Preparation of6-hydroxy-7-isoproproxy-2,2-di-methyl-4-chromanone

In 80 ml of N,N-dimethyl formamide 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 4.1 g(30 millimoles) of potassium carbonate and 4.2 g (2.5 ml, 25 millimoles)of isopropyl iodide are added. The reaction mixture is heated at 130° C.for 6 hours, poured into 200 ml of water and extracted with 100 ml ofcarbon tetrachloride. To the aqueous layer 50 ml of a 5% sodiumhydroxide solution are added and the mixture is cooled below 5° C. Themixture is acidified with concentrated hydrochloric acid, theprecipitated crystalline substance is filtered off and crystallized frommethanol. Thus 4.5 g of the desired compound are obtained, yield 90%,mp.: 138°-139° C.

IR (CCl₄) νCO: 1690 cm⁻¹ ; νOH 3565 cm⁻¹ .

PMR (CDCl₃): 1.48 (12H, m); 2.66 (2H, s); 4.83 (1H); 6.0 (1H, s); 6.54(1H, s); 7.52 (1H, s).

EXAMPLE 20 Preparation of 6-hydroxy-7-sec.butoxy-2,2-dimethyl-4-chromanone

In 100 ml of methyl-ethyl-ketone 4.2 g (20 millimoles) of6,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved and to thesolution thus obtained 4.1 g (30 millimoles) of potassium carbonate, 0.5g of potassium iodide and 3.3 g (2.6 millimoles, 24 millimoles) of sec.butyl bromide are added under stirring. The reaction mixture is heatedto boiling for 12 hours. The reaction mixture is worked up according toExample 17. Thus 4.5 g of the desired compound are obtained, yield 86%,mp.: 114°-116° C.

IR (CCl₄) νCO: 1690 cm⁻¹ ; νOH 3560 cm⁻¹.

PMR (CDCl₃): 0.97 (3H, t, J=6 Hz); 1.32 (3H, d, J=6 Hz); 1.43 (6H, s);1.8 (2H, m); 2.63 (2H, s); 4.4 (1H, m); 6.13 (1H, s); 6.4 (1H s); 7.36(1H, s).

EXAMPLE 21 Preparation of5-hydroxy-7-propargyloxy-2,2-dimethyl-4-chromanone

In 60 ml of methyl-ethyl-ketone 4.2 g of5,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 3.0 g(22 millimoles) of potassium carbonate, 0.2 g of potassium iodide, and3.0 g (2.3 ml, 25 millimoles) of propargyl bromide are added and thereaction mixture is reflexed for 4 hours. The inorganic salt is filteredoff, the residue is taken up in 100 ml of carbon tetrachloride andextracted twice with 25 ml of a 5% sodium hydroxide solution each. Theaqueous-alkaline layer is cooled to 0° C. The aqueous-alkaline layer iscooled to 0° C. The precipitated sodium phenolate salt is filtered off,washed twice with 20 ml of acetone each, and suspended in 25%hydrochloric acid (50 ml). The mixture is stirred at 5° C. for an hour.The precipitated white product is filtered off, washed twice with 20 mlof water each and dried to constant weight. The crude product thusobtained can be directly subjected to further reactions. Thus 3.7 g ofthe desired compound are obtained, yield 75% Mp.: 122°-124° C.

PMR (CDCl₃): 1.44 (6H, s); 2.56 (1H, m); 2.64 (2H, s) 4.64 (2H, d, J=2Hz); 6.0 (2H, m); 12.3 (1H, s).

EXAMPLE 22 Preparation of5-hydroxy-7-isobutoxy-2,2-dimethyl-4-chromanone

In 50 of diethylene glycol dimethylether (DIGLIM) 4.2 g (20 millimoles)of 5,7-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 3.0g (22 millimoles) of potassium carbonate and 0.2 g of potassium iodideand thereafter 3.3 g (2.6 ml, 24 millimoles) of isobutyl bromide areadded. The reaction mixture is heated at 100° C. for 10 hours and workedup according to Example 19. Thus 4.1 g of the desired compound areobtained, yield 79%. Mp.: 77°-79° C.

PMR (CDCl₃): 0.96 (6H, d, J=6 Hz); 1.4 (6H, s); 2.0 (1H, m); 2.6 (2H,s); 3.66 (2H, d, J=6 Hz); 5.9 (2H, m); 12.2 (11H, s).

EXAMPLE 23 Preparation of 7-isopropoxy-8hyroxy-2,2dimenthyl-4-chromanone

In 50 ml of N,N-dimethyl formamide 4.2 g (20 millimoles) of7,8-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 5 ml ofdiethylene glycol dimethylether, 3.0 g (22 millimoles) of potassiumcarbonate and 4.2 g (2.5 ml, 25 millimoles) of isopropyl iodide areadded. The reaction mixture is heated at 140° C. for 4 hours and workedup according to Example 19. Thus 4.5 g of the desired compound areobtained, yield 90%, mp.: 114°-116° C.

PMR (CDCl₃): 1.36 (6H, d, J=6 Hz); 1.46 (6H, s); 2.66 (2H, s); 4.6 (1H,m); 6.0 (1H, s) 6.5 (1H, d, J=8 Hz); 7.34 (1H, d, J=8 Hz).

EXAMPLE 24 Preparation of7-sec.-butoxy-8-hydroxy-2,2-dimethyl-4-chromanone

In 80 ml of dimethyl sulfoxide 4.2 g (20 millimoles) of7.8-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 10 mlof diethylene glycol dimethylether, 4.1 g (30 millimoles) of potassiumcarbonate, 0.5 g of potassium iodide and 3.3 (2.6 ml, 24 millimoles) ofsec. butyl bromide are added. The reaction mixture is heated at 100° C.for 10 hours, poured onto 200 ml of crushed ice and extracted with 100ml of carbon tetrachloride. To the aqueous phase 20 ml of 10% sodiumhydroxide solution are added, the mixture is cooled to 0° C., acidifiedwith concentrated hydrochloric acid and stirred at 0° C. for 2 hours.The product is filtered, washed twice with 20 ml of water, dried andcrystallized from 20% ethanol. Thus 4.4. g of the desired compound areobtained, yield 83%, mp.: 108°-110° C.

PMR (CDCl₃): 0.96 (3H, t, J=8 Hz); 1.3 (3H, d, J=5 Hz); 1.44 (6H, s) 1.7(2H, m); 2.66 (2H, s) 4.3 (1H, m); 5.9 (1H, s); 6.5 (1H, d, J=8 Hz); 7.3(1H, d, J=8 Hz).

PREPARATION OF "MIXED" CHROMANONES OF THE FORMULA III EXAMPLE 25Preparation of 6-ethoxy-7-methoxy-2,2-dimethyl-4-chromanone

In 100 ml of methyl-ethyl-ketone 4.45g (20 millimoles) of6-hydroxy-7-methoxy-2,2-dimethy-4-chromanone are dissolved, whereupon4.1 g (30 millimoles) of potassium carbonate and 4.7 g (2.4 ml, 30millimoles) of ethyl iodide are added and the reaction mixture isrefluxed for 5 hours. The precipitated inorganic salt is filtered off,washed twice with 20 ml of acetone each and the solvent is removed. Theresidue is crystallized from 90% ethanol. Thus 4.75 g of the desiredcompound are obtained, yield 95%. Mp.: 86°-87° C.

PMR (CDCl₃): 1.44 (9H, s+t, J=6 Hz); 2.68 (2H, s); 3.92 (3H, s); 4.14(2H, q, J=6 Hz); 6.44 (1H, s); 7.32 (1H, s).

EXAMPLE 26 Preparation of 6-methoxy-7-ethoxy-2,2-dimethyl-4-chromanone

In 100 ml of acetone 4.7 g (20 millimoles) of6-hydroxy-7-ethoxy-2,2-dimethyl-4-chromanone are dissolved, whereupon4.1 g (30 millimoles) of potassium carbonate and 4.5 b (2 ml, 30millimoles) of methyl iodide are added. The reaction mixture is refluxedfor 4 hours, the inorganic salt is filtered off, washed twice with 20 mlof acetone and the half of the solvent is removed. The residue is cooledto 0° C., the precipitated product is filtered off and dried to constantweight. Thus 4.6 g of the desired compound are obtained, yield 92%. Mp.:120°-122° C.

PMR (CDCl₃): 1.5 (9H, m); 2.64 (2H, s); 3.86 (3H, s); 4.16 (2H, q, J=8Hz); 6.4 (1H s); 7.32 (1H, s).

EXAMPLE 27 Preparation of 6-methoxy-7sec.butoxy-2,2-dimethyl-4-chromanone

In 40 ml of a 5% sodium hydroxide solution 5.2 g (20 -millimoles) of6-hydroxy-7-sec. butoxy-2,2-dimethyl-4-chromanone are dissolvedwhereupon 80 ml of dichloro methane and 0.5 g of triethyl benzylammonium chloride are added and the mixture is intensively stirred atroom temperature for 30 minutes. After the addition of 4.25 g (1.9 ml,30 millimoles) of methyl iodide the reaction mixture is stirred foranother 2 hours. The organic phase is separated, washed twice with 50 mlof water each, dried over sodium sulfate and the solvent is removed. Theresidue is crystallized from 90% ethanol. Thus 5.34 g of the desiredcompound are obtained, yield 96%. Mp.: 92.5°-93° C.

PMR (CDCl₃): 0.96 (3H, t, J=6 Hz); 1.34 (3H, d, J=4 Hz); 1.4 (6H, s);1.7 (2H, m); 2.6 (2H, s); 3.8 (3H, s); 4.3 (1H, m); 6.36 (1H, s); 7.22(1H, s).

EXAMPLE 28 Preparation of 5-methoxy-7-sec.butoxy-2,2-dimethyl-4-chromanone

In 100 ml of acetonitrile 5.6 g (20 millimoles) of the sodium salt of5-hydroxy-7-sec. butoxy-2,2-dimethyl-4-chromanone are dissolved andstirred in the presence of 0.5 g (2 millimoles) 18-Crown-6 for 30minutes. Thereafter 4.25 g (1.9 ml, 30 millimoles) of methyl iodide areadded and the reaction mixture is stirred for another 3 hours. Theinorganic salt is filtered off, the solvent removed and the residuesuspended in carbon tetrachloride, extracted twice with 30 ml of watereach, the organic phase is dried over sodium sulfate and evaporated.Thus 5.1 g of the desired compound are obtained in the form of a lightyellow oil, yield 92%.

PMR (CDCl₃):

0.96 (3H, t, J=7 Hz); 1.3 (3H, d, J=8 Hz); 1.44 (6H, s); 1.7 (2H, m);2.6 (2H, s); 3.85 (3H, s); 4.3 (1H, m); 6.0 (2H, m).

EXAMPLE 29 Preparation of7-isobutoxy-8-methoxy-2,2-dimethyl-4-chromanone

In 50 ml of a 10% sodium hydroxide solution under nitrogen 5.2 g (20millimoles) of 7-isobutoxy-8-hydroxy-2,2,-dimethyl-4-chromanone aredissolved, whereupon 2.6 g (2 ml, 21 millimoles) of dimethyl sulfate areadded and the reaction mixture is intensively stirred for 3 hours at 50°C. The mixture is diluted with 100 ml of ice cold water, extracted threetimes with 50 ml of chloroform each, the organic phase is washed twicewith 40 ml of water dried over sodium sulfate and the solvent isevaporated. Thus 5.2 g of the desired compound are obtained in the formof yellow oil, yield 93%.

PMR (CDClphd 3): 0.96 (6H, dd, J=8 Hz); 1.4 (6H, s); 2.1 (1H, m); 2.6(2H, s); 3.8 (3H, s) 3.88 (2H, m); 6.5 (1H, d, J=8 Hz); 7.56 (1H, d, J=8Hz).

Preparation of 2H-chromenes of the Formula V EXAMPLE 30 Preparation of7-methoxy-2,2-dimethyl-2H-chromene (P1)

A mixture of 2.1 g (10 millimoles) of7-methoxy-2,2-dimethyl-4-chromanone, 50 ml of tetrahydrofuran, 20 ml ofwater, 2.66 g (15 millimoles) of palladium chloride and 4.2 g (0.11mole) of sodium tetrahydro borate is stirred at 0° C for 20 minutes andthereafter at 5° C. for a further 4 hours. The reaction mixture isfiltered, the filtrate extracted twice with 50 ml of chloroform each.The solvent is distilled off, the residue taken up in 50 ml of tolueneand distilled in the presence of anhydrous potassium hydrogen sulfatefor 20 minutes. The reaction having been completed the organic phase iswashed twice with 20 ml of water each and the solvent is removed. Thecrude product is purified by column chromatography. Thus 1.75 g of thedesired compound are obtained in the form of a colorless oil, yield 85%.

PMR (CDCl₃): 1.36 (6H, s); 3.64 (3H, s); 5.36 (1H, d, J=10 Hz); 6.16(1H, d, J=10 Hz); 6.3 2H, m) 6.76 (1H, d, J=8 Hz).

EXAMPLE 31 Preparation of 6,7-dimethoxy-2,2-dimethyl-2H-chromene (P2)

In a mixture of 75 ml of tetrahydrofurane and 25 ml of ethanol 4.7 g (20millimoles) 6.7-dimethoxy-2,2-dimethyl-4-chromanone are dissolved,whereupon 1.5 g (40 millimoles) of sodium tetrahydro borate are added insmall portions. The reaction mixture is heated to boiling for an hour,cooled to 15° C., whereupon 50 ml of 4N hydrochloric acid are added andthe mixture is stirred at a temperature not exceeding 20° C. for 30minutes. The two-phase layer is separated, the aqueous phase isextracted twice with 40 ml of petrol ether (30°-40° C.) each, theorganic phases are collected, washed twice with 25 ml of 5% sodiumhydroxide solution and twice with 40 ml water each, dried over sodiumsulfate and evaporated. The residue is crystallized from 80% methanol.Thus 4.0 g of the desired compound are obtained, yield 92%. Mp.: 46°-47°C.

PMR (CCl₄): 1.34 (6H, s); 3.69 (3H, s); 3.72 (3H, s) 5.38 (1H, d, J=10Hz); 6.18 (1H, d, J=10 Hz); 6.36 (1H, s); 6.48 (1H, s).

EXAMPLE 32 Preparation of 6-methoxy-7-ethoxy-2,2-dimethyl-2H-chromeme(P3)

In 80 ml of anhydrous tetrahydrofurane 5.0 g (20 millimoles ) of6-methoxy-7-2,2-dimethyl-4-chromanone are dissolved whereupon 1.5 g oflithium aluminum hydride are added in small portions under stirring andthe reaction mixture is heated to boiling for an hour. The reactionmixture is worked up according to Example 31. The product is purified bycolumn chromatography. Thus 4.1 g of the desired compound are obtainedin the form of a colorless oil, yield 88%.

PMR (CDCl₃): 1.45 (9H, m); 3.8 (3H, s); 4.1 (2H, q, J=8 Hz); 5.48 (1H,d, J=10 Hz) 6.28 (1H, d, J=10 Hz); 6.46 (1H, s); 6.6 (1H, s).

EXAMPLE 33 Preparation of 5-methoxy-7-sec.butoxy-2,2-dimethyl-2H-chromene

In a mixture of 60 ml of tetrahydrofuran and 40 ml of methanol 5.6 g (20millimoles) of 5-methoxy-7-sec. butoxy-2,2-dimethyl-4-chromanone aredissolved, whereupon 1.5 g (40 millimoles) of sodium tetrahydroborateare added in small portions and the reaction mixture is heated toboiling for 2 hours. The reaction mixture is worked up according toExample 31. The product is purified by column chromatography. Thus 4.4 gof the desired compound are obtained in the form of a light yellow oil,yield 85%.

PMR (CDCl₃): 0.92 (3H, t, J=8 Hz); 1.24 (3H, d, J=8 Hz); 1.36 (6H, s);1.6 (2H, m); 3.7 (3H, s); 4.2 (1H, m); 5.3 (1H, d, J=10 Hz); 5.92 (2H,m); 6.5 (1H, d, J=10 Hz).

EXAMPLE 34 Preparation of 7sec. butoxy-8-methoxy-2,2-dimethyl-2chromene

In 100 ml of tetrahydrofuran 5.6 g (20 millimoles) of 7-sec.butoxy-8-methoxy-2,2-dimethyl-4-chromanone are dissolved. To thesolution 1.5 g of lithium aluminum hydride are added in small portionsunder stirring and the reaction mixture is heated to boiling for 2hours. The reaction mixture is worked up according to Example 31. Theproduct is purified by column chromatography. This 4.2 g of the desiredcompound in the form of a colorless oil, yield 80%.

PMR (CDCl₃): 0.96 (3H, t, J=8 Hz); 1.24 (3H, d, J=8 Hz); 1.4 (6H, s);1.7 (2H, m); 3.76 (3H, s); 4.2 (1H, m); 5.4 (1H, d, J=10 Hz), 6.16 (1H,d, J=10 Hz); 6.32 (1H, d, J=8 Hz); 6.56 (1H, d, J=8 Hz).

Remarks: The conditions used at column chromatography are as follows:

adsorbent: Kieselgel-60

eluent: a 9:1 mixture of hexane and ether.

EXAMPLES 35-188

The new compounds enumerated in Table II and the known compoundsdisclosed in Table III are prepared by the processes according to theprevious Examples [Compounds III/1 and III/2 serve as referencecompound]

                                      TABLE II                                    __________________________________________________________________________    Compounds of the Formula V                                                     ##STR9##                                  (V')                               No.                                                                              R.sub.1                                                                          R.sub.2                                                                          R.sub.3                                                                          R.sub.4                                                                          R.sub.5                                                                          R.sub.6   R.sub.7   R.sub.8                                 __________________________________________________________________________    1  Me Me H  H  H  H         nPrO      H  TT-35                                2  Me Me H  H  H  H         iPrO      H  TT-36                                3  Me Me H  H  H  H         iBuO      H  TT-39                                4  Me Me H  H  H  H         c-pentyl-O                                                                              H  TT-40                                5  Me Me H  H  H  H         CH.sub.3OCH.sub.2O                                                                      H  TT-77                                6  Me Me H  H  H  H         CH.sub.3SCH.sub.2O                                                                      H                                       7  Me Me H  H  H  H         EtOCH.sub.2O                                                                            H  TT-78                                8  Me Me H  H  H  H         crotyl-O  H                                       9  Me Me H  H  H  H         prenyl-O  H                                       10 Me Me H  H  H  H         benzyl-O  H  TT-41                                11 Me Me H  H  Me H         EtO       H  TT-52                                12 Me Me H  H  Me H         nPrO      H  TT-53                                13 Me Me H  H  Me H         iPrO      H  TT-54                                14 Me Me H  H  Me H         nBuO      H                                       15 Me Me H  H  Me H         sec.BuO   H  TT-55                                16 Me Me H  H  Me H         iBuO      H  TT-56                                17 Me Me H  H  Me H         c-pentyl-O                                                                              H  TT-57                                18 Me Me H  H  Me H         benzyl-O  H                                       19 Me Me H  H  Me H         CH.sub.3OCH.sub.2O                                                                      H                                       20 Me Me H  H  Me H         CH.sub.3SCH.sub.2O                                                                      H                                       21 Me Me H  H  Me H         EtOCH.sub.2O                                                                            H                                       22 Me Me H  H  Me H         CHCCH.sub.2O                                                                            H  TT-58                                23 Me Me H  H  H  H         EtO       Me                                      24 Me Me H  H  H  H         iPrO      Me                                      25 Me Me H  H  H  H         sec.BuO   Me                                      26 Me Me H  H  H  H         iBuO      Me                                      27 Me Me H  H  H  H         CH.sub.3OCH.sub.2O                                                                      Me                                      28 Me Me H  H  H  H         CH.sub.3SCH.sub.2O                                                                      Me                                      29 Me Me H  H  H  H         EtOCH.sub.2O                                                                            Me                                      30 Me Me H  H  H  H         CHCCH.sub.2O                                                                            Me                                      31 Me Me H  H  H  iBuO      iBuO      H  TT-19                                32 Me Me H  H  H  benzyl-O  benzyl-O  H  TT-20                                33 Me Me H  H  H  CF.sub.3 CH.sub.2O                                                                      OF.sub.3 CH.sub.2O                                                                      H  TT-15                                34 Me Me H  H  H  allyl-O   allyl-O   H  TT-08                                35 Me Me H  H  H  crotyl-O  crotyl-O  H  TT-12                                36 Me Me H  H  H  prenyl-O  prenyl-O  H  TT-13                                37 Me Me H  H  H  CHCCH.sub.2O                                                                            CHCCH.sub.2O                                                                            H                                       38 Me Me Cl Cl H  EtO       EtO       H  TT-27                                39 Me Me Cl Cl H  iPrO      iPrO      H  TT-28                                40 Me Me Cl Cl H  MeO       EtO       H  TT-30                                41 Me Me Cl Cl H  MeO       iPrO      H  TT-31                                42 Me Me H  H  H  MeO       sec.BuO   H  TT-23                                43 Me Me H  H  H  MeO       iBuO      H  TT-24                                44 Me Me H  H  H  MeO       c-pentyl-O                                                                              H  TT-43                                45 Me Me H  H  H  MeO       benzyl-O  H  TT-25                                46 Me Me H  H  H  O(CH.sub.3).sub.2 CO                                                                              H  TT-87                                47 Me Me H  H  H  MeO       Krotyl-O  H                                       48 Me Me H  H  H  MeO       prenyl-O  H  TT-14                                49 Me Me H  H  MeO                                                                              H         EtO       H  TT-59                                50 Me Me H  H  MeO                                                                              H         nPrO      H  TT-60                                51 Me Me H  H  MeO                                                                              H         iPrO      H  TT-61                                52 Me Me H  H  MeO                                                                              H         sec.BuO   H  TT-62                                53 Me Me H  H  MeO                                                                              H         iBuO      H  TT-63                                54 Me Me H  H  H  H         EtO       MeO                                                                              TT-64                                55 Me Me H  H  H  H         nPrO      MeO                                                                              TT-65                                56 Me Me H  H  H  H         iPrO      MeO                                                                              TT-66                                57 Me Me H  H  H  H         sec.BuO   MeO                                                                              TT-67                                58 Me Me H  H  H  H         iBuO      MeO                                                                              TT-68                                59 Me H  Me H  H  MeO       MeO       H  TT-72                                60 Me H  Me H  MeO                                                                              H         MeO       H                                       61 Me H  Me H  H  H         MeO       MeO                                     62 Me H  Me H  Me H         MeO       H                                       63 Me H  Me H  H  H         MeO       Me                                      64 Me H  Me H  H  H         MeO       H                                       65 Me H  Me H  H  MeO       EtO       H                                       66 Me H  Me H  H  MeO       nPrO      H                                       67 Me H  Me H  H  MeO       iPrO      H                                       68 Me H  Me H  H  MeO       sec.BuO   H                                       69 Me H  Me H  H  MeO       iBuO      H                                       70 Me H  Me H  H  MeO       CHCCH.sub.2O                                                                            H                                       71 Me Me H  Me H  MeO       EtOOCCH.sub.2O                                                                          H                                       72 Me Me H  Me H  MeO       benzyl-O  H                                       73 Me Me H  Me H  benzyl-O  benzyl-O  H                                       __________________________________________________________________________

                                      TABLE III                                   __________________________________________________________________________    Compounds of the Formula V                                                    No.                                                                              R.sub.1                                                                          R.sub.2   R.sub.3                                                                          R.sub.4                                                                          R.sub.5                                                                            R.sub.6    R.sub.7    R.sub.8                      __________________________________________________________________________    1  H  H         H  H  H    H          H          H                            2  Me Me        H  H  H    H          H          H                            3  Me Me        H  H  MeO  H          H          H                            4  Me Me        H  H  H    MeO        H          H                            5  Me Me        H  H  H    H          MeO        H                            6  Me Me        H  H  H    H          H          MeO                          7  Me Me        H  H  HOC  H          H          H                            8  Me Me        H  H  H.sub.3 COC                                                                        H          H          H                            9  Me Me        H  H  H    EtO        H          H                            10 Me Me        H  H  H    nPrO       H          H                            11 Me Me        H  H  H    nBuO       H          H                            12 Me Me        H  H  H    CH.sub.3 CO                                                                              H          H                            13 Me Me        H  H  H                                                                                   ##STR10## H          H                            14 Me Me        H  H  H    H          EtO        H                            15 Me Me        H  H  H    H          nBuO       H                            16 Me Me        H  H  H    H          sec.BuOn   H                            17 Me Me        H  H  H    H          tBuO       H                            18 Me Me        H  H  H    H          nPentO     H                            19 Me Me        H  H  H    H          EtO(CH.sub.2).sub.2 O                                                                    H                            20 Me Me        H  H  H    H          CHCCH.sub.2O                                                                             H                            21 Me Me        H  H  H    H          HOC        H                            22 Me Me        H  H  H    H          H.sub.3 COC                                                                              H                            23 Me Me        H  H  H    H          CH.sub.3 CCCH.sub.2O                                                                     H                            24 Me Me        H  H  H    H          CH.sub.2CHCH.sub.2O                                                                      H                            25 Me Me        H  H  H    H          CF.sub.3 CH.sub.2 O                                                                      H                            26 Me Me        H  H  H    Br         MeO        H                            27 Me Me        H  H  H    Br         EtO        H                            28 H  H         H  H  H    MeO        MeO        H                            29 H  Me        H  H  H    MeO        MeO        H                            30 Me Me        H  H  H    MeO        MeO        H                            31 Me Et        H  H  H    MeO        MeO        H                            32 Et Et        H  H  H    MeO        MeO        H                            33 H                                                                                 ##STR11##                                                                              H  H  H    MeO        MeO        H                            34 Me                                                                                ##STR12##                                                                              H  H  H    MeO        MeO        H                            35 Me CF.sub.3  H  H  H    MeO        MeO        H                            36 Me Me        H  H  H    EtO        EtO        H                            37 Me Me        H  H  H    nPrO       nPrO       H                            38 Me Me        H  H  H    iPrO       iPrO       H                            39 Me Me        H  H  H    nBuO       nBuO       H                            40 Me Me        H  H  H    sec.BuO    sec.BuO    H                            41 Me Me        H  H  H    tBuO       tBuO       H                            42 Me Me        H  H  H    nPentO     nPentO     H                            43 Me Me        H  H  H    MeO        EtO        H                            44 Me Me        H  H  H    EtO        MeO        H                            45 Me Me        H  H  H    MeO        iPrO       H                            46 Me Me        H  H  H    iPrO       MeO        H                            47 Me Me        H  H  H    MeO        nPrO       H                            48 Me Me        H  H  H    MeO        nBuO       H                            49 Me Me        H  H  H    MeO        nHexO      H                            50 Me Me        H  H  H    OCH.sub.2O            H                            51 Me Me        H  H  H    O(CH.sub.2)O          H                            52 Me Me        H  H  H    CHCOCH.sub.2O                                                                            MeO        H                            53 Me Me        H  H  H    CH.sub.2CHCH.sub.2O                                                                      MeO        H                            54 Me Me        H  H  H    MeO        CHCCH.sub.2O                                                                             H                            55 Me Me        H  H  H    MeO        CH.sub.2CHCH.sub.2O                                                                      H                            56 Me Me        H  H  H    MeO        CF.sub.3 CH.sub.2O                                                                       H                            57 Me Me        H  H  H    CF.sub.3 CH.sub.2O                                                                       MeO        H                            58 Me Me        H  H  H    MeO        MeO        H                            59 Me Me        H  H  MeO  MeO        H          H                            60 Me Me        H  H  MeO  H          MeO        H                            61 Me Me        H  H  H    MeO        H          MeO                          62 Me Me        H  H  H    H          MeO        Me                           63 Me Me        H  H  MeO  MeO        MeO        H                            64 Me Me        H  H  MeO  H          MeO        CH.sub.3 CO                  65 Me Me        H  H  MeO  CH.sub.3 COO                                                                             MeO        H                            66 Me Me        H  H  MeO  H          Me         CH.sub.3 COO                 67 H  H         Me H  H    MeO        MeO        H                            68 Me Me        H  Me H    MeO        MeO        H                            69 Me Me        H  H  Me   H          MeO        H                            70 Me Me        Cl Cl H    H          H          H                            71 Me Me        Cl Cl H    MeO        H          H                            72 Me Me        Cl Cl H    H          MeO        H                            73 Me Me        Cl Cl H    MeO        MeO        H                            74 Me Me        Cl Cl H    OCH.sub.2O            H                            75 Me Me        F  H  H    MeO        MeO        H                            76 Me Me        F  H  H    OCH.sub.2O            H                            77 Me Me        F  H  MeO  H          H          H                            78 Me Me        F  H  H    H          MeO        H                            79 Me Me        F  H  Me   H          Me         H                            80 Me Me        F  H  H    CH.sub.3 CO                                                                              H          H                            81 Me Me        F  H  OH   CH.sub.3 CO                                                                              H          H                            __________________________________________________________________________

EXAMPLE 189 Preparation of 50 EC formulation of the active ingredient

    ______________________________________                                        Component               Amount                                                ______________________________________                                        Active ingredient of the Formula V                                                                    500     g.sup.x                                       "Arylan" C.A.           64,2    g                                             "Lubrol" N 15           40,0    g                                             Aromasol filled up to   1000.0  ml                                            ______________________________________                                         .sup.x related to 100% of active ingredient                              

Remark: The above composition is diluted with water and the spray thusobtained is used for testing the activity of the compounds of thegeneral Formula V.

The chromene derivatives enumerated in Tables II and III can be preparedin analogous manner to Examples 1-34.

EXAMPLE 190 Determined of insecticidal and nematocidal effect ofcompounds of the Formula V Test Pests

Insects:

cotton bug (Dysdercus fasciatus)

cabbage butterfly (Pieris brassicae)

mustard beetle

domestic fly (Musca domestica)

pea plant-louse (Acirtosypon pisi)

Colorado beetle

Nematodes:

Caenorhabditis elegans

tomato root gall nematode (Meloidogyne incognita)

The details of the tests used are disclosed below.

(1) Cotton bug test

A dilution series is prepared from the test compound with acetone and0.2 μl of each dilution is topically applied onto the back part oflarvae of the II. stage of growth with the aid of a Hamiltion syringe.The active ingredient is absorbed through the cuticula. The animals arekept in a large glass and fed with cotton grains and water. After adultshedding the surviving insects are observed for eventual adultoidsymptoms, the egg-reproduction and the development of the ovules isevaluated too.

(2) Cabbage butterfly

From the 50 EC of the test compound a diluted series is prepared withwater and the host seedlings (cabbage) are sprayed with this compositionuntil the spray runs down. The spray is allowed to dry whereupon 20young larvae of the II. stage are placed on each treated plant and theseedlings are kept under so-called "long-day" illumination (18 hours ofillumination and 6 hours of darkness). The nibbled plants are replacedby similarly sprayed plants if necessary. The killing rate of theinsects, the growth rate of the larvae and the morphologicaldeformations of the surviving nymphs and adults are registered.

(3) Mustard beetle

Two weeks' old mustard seedlings are sprayed with a solution of 0.1 g ofthe test compound, 0.5 ml of dimethyl sulfoxide, and 10 μl of 50 ECcomposition in 10 ml of water. After the spray is dried, 20 mustardlarvae of the II. stage are placed on each plant. The sprayed plants arecharged every second day. The evaluation is based on the number of theimagos hatching from the nymphs.

(4) Domestic fly

The fly larvae are grown on a nutrient medium of the followingcomposition: 2 ml of milk; 2 ml of water; 2 g of wheat bran; 0.1 ml ofsaturated alcoholic nipagin solution.

The nutrient medium is filled into cylindrical glass vials (30×100 mm)and 25 fly larvae are raised in each vial. The test compound isdissolved in milk; the end concentration (related to milk) amounts to0.1% which corresponds to 0.05% (related to the total nutrient medium).The solution of the active ingredient is admixed with the nutrientmedium whereupon 25 ml of domestic fly larvae of the I. stage are placedinto each vial and the vials are closed with a hard cotton-wool stopper.The nymphs emerging from the larvae are collected in each vial, countedand kept in a Petri dish (diameter 25 mm) until flies hatch from thenymphs. The hatched flies are counted.

(5) Caenorhabditis elegans

0.5 ml of the acetonous solution of the test compound is applied onto aNGM agar plate free from bacteria in a Petri dish. After the acetone hasdried 25-30 young adults are placed on the plate. After 24 hours thesurviving and killed insects are counted.

(6) Root gall nematode

The test is carried out on II. stage infective larvae, which arecollected from the root of tomato plant, placed on a filter andincubated in sterile water at 25° C. The hatched larvae are collectedevery 24 hours and immediately placed onto the treated nutrient medium.As nutrient medium NGM agar plate free from bacterial is used. 0.5 ml ofthe acetoneous solution of the test compound is applied onto the surfaceof the plate in a Petri-dish. After the acetone has evaporated 5 μl ofthe larva suspension is applied onto each plate. After 72 hours thesurviving and killed insects are counted.

The test results are summarized in the following Tables.

(Remark: in the cotton bug test 50 insects are used).

In each Table the results obtained with the control group are disclosedas well.

The following test compounds are used in the biological experiments.

                  TABLE IV                                                        ______________________________________                                         ##STR13##                                                                    No.      R.sup.5 O    R.sup.6 O    R.sup.4                                    ______________________________________                                        1        6 MeO        7 MeO        H                                          2        6 EtO        7 EtO        H                                          3        6 MeO        7 EtO        H                                          4        6 OCH.sub.2O 7        H                                              5        6 allylO     7 allylO     H                                          6        6 iPrO       7 iPrO       H                                          7        6 MeO        7 allylO     H                                          8        6 MeO        7 iPrO                                                  9        6 crotylO    7 crotylO    H                                          10       6 prenylO    7 prenylO    H                                          11       6 MeO        7 prenylO    H                                          12       6 CF.sub.3 CH.sub.2 O                                                                      7 CF.sub.3 CH.sub.2 O                                                                      H                                          13       6 nPrO       7 nPrO       H                                          14       6 nBuO       7 nBuO       H                                          15       6 sec.BuO    7 sec.BuO    H                                          16       6 iBuO       7 iBuO       H                                          17       6 benzylO    7 benzylO    H                                          18       6 MeO        7 nPrO       H                                          19       6 MeO        7 nBuO       H                                          20       6 MeO        7 sec.BuO    H                                          21       6 MeO        7 iBuO       H                                          22       6 MeO        7 benzylO    H                                          23       H            7 MeO        H                                          24       H            7 EtO        H                                          25       H            7 nPrO       H                                          26       H            7 iPrO       H                                          27       H            7 nBuO       H                                          28       H            7 sec.BuO    H                                          29       H            7 iBuO       H                                          30       H            7 c-pentylO  H                                          31       H            7 benzylO    H                                          32       H            7 MeO        5 Me                                       33       6 MeO        7 c-pentylO  H                                          34       6 EtO        7 MeO        H                                          35       7 MeO        8 MeO        H                                          36       5 MeO        7 MeO        H                                          37       H            7 propargylO H                                          38       H            7 EtO        5 Me                                       39       H            7 nPrO       5 Me                                       40       H            7 iPrO       5 Me                                       41       H            7 sec.BuO    5 Me                                       42       H            7 iBuO       5 Me                                       43       H            7 c-pentylO  5 Me                                       44       H            7 propargylO 5 Me                                       45       5 MeO        7 EtO        H                                          46       5 MeO        7 nPrO       H                                          47       5 MeO        7 iPrO       H                                          48       5 MeO        7 sec.BuO    H                                          49       5 MeO        7 iBuO       H                                          50       7 EtO        8 MeO        H                                          51       7 nPrO       8 MeO        H                                          52       7 iPrO       8 MeO        H                                          53       7 sec.BuO    8 MeO        H                                          54       7 iBuO       8 MeO        H                                          55       H            H            H                                           56      6 O(CH.sub.3).sub.2 CO 7                                                                            H                                              ______________________________________                                    

Tables V Biological results

                  TABLE V/1                                                       ______________________________________                                        Effect of the test compounds on cotton bug                                                                    Sterilizing                                   Test      LD.sub.50   AJH effect                                                                              effect                                        compound  (μg/insect)                                                                            (μg/insect)                                                                          (μg/insect)                                ______________________________________                                         1 (P2)   0.6         1         10                                             3        0.5         10        10                                             8        0.45        1         0.2                                           10        0.6         --        --                                            20        0.4         0.1       --                                            21        0.4         --        --                                            control.sup.+                                                                           --          --        --                                            ______________________________________                                         .sup.+  = when the insects are treated with acetone, the survival rate is     90-95%.                                                                  

                  TABLE V/2                                                       ______________________________________                                        Effect of the test compound on cabbage butterfly                                         Killing rate  Survival                                             Test       of larvae     nymph   adult                                        compound   %             %       %                                            ______________________________________                                        23 (P1)    41            59      50                                           25         52            48      39                                           38         81            19      19                                           41         11            19      14                                           42         100           --      --                                           43         100           --      --                                           44         83            17      17                                           46         88            12      12                                           47         87            13      9                                            48         100           --      --                                           49         100           --      --                                           50         76            24      24                                           51         100           --      --                                           52         64            36      32                                           53         100           --      --                                           54         93            7       7                                            control.sup.x                                                                            12            88      88                                           ______________________________________                                         .sup.+  = EC composition containing no active ingredient                 

In the 50 EC compositions the concentration of compounds 23 and 25amounts to 0.01% and that of the other compounds to 0.1%.

                  TABLE V/3                                                       ______________________________________                                        Effect of the test compounds on mustard beetle                                Test                                                                          compound    Concentration                                                                             Survival, adults (%)                                  ______________________________________                                        42          1%          27                                                    51          1%          45                                                    control     0%          100                                                   ______________________________________                                    

                  TABLE V/4                                                       ______________________________________                                        Effect of the test compounds on domestic fly                                  Test           Survival                                                       compound       nymph (%) adult (%)                                            ______________________________________                                        23 (P1)        100       33.3                                                 28             115       25.6                                                 29             100       28.2                                                 34             85        12.8                                                 35             12        0                                                    38             40        14.8                                                 40             50.9      27.6                                                 41             25.4      12.5                                                 42             45.4      25.5                                                 43             52.7      31.8                                                 44             50.9      10.6                                                 46             9.1       6.4                                                  49             0         0                                                    50             5.4       4.2                                                  51             12        0                                                    52             12        0                                                    Control        100       100                                                  ______________________________________                                    

                  TABLE V/5                                                       ______________________________________                                        Effect of the test compounds on adult Caenorhabditis                          elegans nematodes                                                                     Concen-          Size of                                              Test    tration Lethality                                                                              descendant                                           compound                                                                              μg/ml                                                                              %        population Remarks                                   ______________________________________                                         1 (P2) 200     100      no descendants                                               400     100      no descendants                                        3 (P3) 200     70       some descendants                                             400     90       no descendants                                        4      100     100      no descendants                                               200     100      no descendants                                               400     100      no descendants                                        5      200     40       some descendants                                             400     90       no descendants                                        7      200     90       no descendants                                               400     90       no descendants                                        8      200     70       reduced                                                      400     80       no descendants                                        14     200     30       reduced                                                      400     80       reduced                                              23 (P1) 200     44       reduced                                                      400     98       no descendants                                       34      200     15       reduced    paralysation                                      400     23       some descendants                                                                         paralysation                              35      200     67       reduced    paralysation                                      400     100      no descendants                                                                           paralysation                              37      200     100      no descendants                                                                           paralysation                                      400     100      no descendants                                                                           paralysation                              44      200     20       some descendants                                                                         paralysation                                      400     30       no descendants                                                                           paralysation                              50      200     40       reduced                                                      400     100      no descendants                                       52      200     60       reduced                                                      400     73       reduced                                              53      200     25       reduced                                                      400     85       reduced                                              Control --       0       normal                                               10%     --       0       normal                                               acetone                                                                       ______________________________________                                    

                  TABLE V/6                                                       ______________________________________                                        Effect of test compounds on tomato root gall nematodes                        (mortality %)                                                                           1.     2.                                                                           (in parentheses                                                               the number of                                                                 individual is                                                 Test    Dose    disclosed)   Average                                                                              Nematocidal                               compound                                                                              μg/ml                                                                              %        %     %      effect                                  ______________________________________                                        1 (P2)  400     98 (65)  95 (55)                                                                             97     strong                                          200     76 (42)  76 (42)                                                                             76     strong                                  2       400     83 (40)  90 (20)                                                                             87     strong                                          200     74 (38)  69 (32)                                                                             72     strong                                  3 (P3)  400     100 (13) 95 (40)                                                                             97     strong                                          200     24 (62)  20 (50)                                                                             22     --                                      4       400     96 (65)  92 (60)                                                                             94     strong                                          200     84 (45)  69 (70)                                                                             77     strong                                  5       400     45 (31)  43 (56)                                                                             44     medial                                  acetone 200     18 (11)  29 (21)                                                                             23     --                                      10%              3 (56)   0 (28)                                                                             1.5    inactive                                Control          0 (41)   6 (49)                                                                              2     inactive                                NGM              0 (40)   3 (48)                                              ______________________________________                                    

What we claim is:
 1. A process for the preparation of a compound of theFormula (II) ##STR14## wherein R¹ and R² are each independentlyhydrogen, C₁ to C₆ or halogen-substituted C₁ to C₆ alkyl;R³ is hydrogen,halogen, or C₁ to C₆ alkyl; and R⁵ is alkyl, alkenyl or alkynyl, whichcomprises the step of selectively etherifying a compound of the Formula(I) ##STR15## in the 7-position with an approximately equal molar amountof an alkyl, alkenyl or alkynyl halide, in the presence of a base, acatalyst and a solvent.
 2. The process defined in claim 1 wherein inFormula (II) R¹ and R² are each methyl, R³ is hydrogen, and R⁵ is C₁ toC₄ alkyl.
 3. The process defined in claim 1 which comprises usingpotassium iodide as the catalyst, and potassium carbonate, sodiumcarbonate, potassium hydroxide or sodium hydroxide as the base.
 4. Theprocess defined in claim 1 which comprises using acetone, methyl ethylketone, methanol, ethanol, water, dimethyl formamide, dimethylsulfoxide, or a mixture thereof as solvent.
 5. The process defined inclaim 1 which comprises using water, aqueous sodium hydroxide,acetonitrile, chloroform, dichloromethane, tetrachlorethylene, carbontetrachloride, diethylene glycol, diethyl ether or a mixture thereof assolvent.
 6. A process for the preparation of a compound of the Formula(V) ##STR16## wherein R¹ and R² are each hydrogen C₁ to C₆ orhalogen-substituted C₁ to C₆ alkyl;R₃ is hydrogen, halogen or C₁ to C₆alkyl; R⁵ and R⁶ are each alkyl, alkenyl or alkynyl, with the provisothat R⁵ and R⁶ are never identical; which comprises the steps of:(a)selectively etherifying a compound of the Formula (I) ##STR17## in the7-position with an approximately equal molar amount of an alkyl,alkenyl, or alkynyl halide, in the presence of a base, a catalyst, and asolvent to yield a compound of the Formula (II) ##STR18## (b)etherifying the compound of the Formula (II) with an approximately equalmolar amount of an alkyl, alkenyl, or alkynyl halide or with a dialkylsulfate, having an alkyl, alkenyl or alkynyl moiety different from thatof the etherifying compound employed during step (a), to yield acompound of the Formula (III) ##STR19## (c) reducing the compound of theFormula (III) with lithium aluminum hydride or sodium borohydridereducing agent to yield a compound of the Formula (IV) ##STR20## and (d)dehydrating the compound of the Formula (IV) to yield the compound ofthe Formula (V).
 7. The process defined in claim 6 wherein in Formula(V) R¹ and R² are each methyl, R³ is hydrogen, R⁵ is C₁ to C₄ alkyl, andR⁶ is C₁ to C₄ alkyl.
 8. The process defined in claim 6 which comprisesaccording to step (a) using potassium iodide as the catalyst, andpotassium carbonate, sodium carbonate, potassium hydroxide or sodiumhydroxide as the base.
 9. The process defined in claim 6 which comprisesaccording to step (a) using water, aqueous hydroxide, acetonitrile,chloroform, dichloromethane, tetrachloroethylene, carbon tetrachloride,diethylene glycol, diethyl ether, or a mixture thereof as solvent. 10.The process defined in claim 6 which comprises according to step (b)using a phase transfer catalyst selected from the group consisting oftriethyl benzyl ammonium chloride and 18-Crown-6.